一系列噻吩扩展三环嘌呤 2'-脱氧核苷类似物的合成与生物评价。
Synthesis and biological evaluation of a series of thieno-expanded tricyclic purine 2'-deoxy nucleoside analogues.
机构信息
Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA.
出版信息
Bioorg Med Chem. 2012 May 1;20(9):3009-15. doi: 10.1016/j.bmc.2012.03.004. Epub 2012 Mar 12.
Abstract
Introducing structural diversity into the nucleoside scaffold for use as potential chemotherapeutics has long been considered an important approach to drug design. In that regard, we have designed and synthesized a number of innovative 2'-deoxy expanded nucleosides where a heteroaromatic thiophene spacer ring has been inserted in between the imidazole and pyrimidine ring systems of the natural purine scaffold. The synthetic efforts towards realizing the expanded 2'-deoxy-guanosine and -adenosine tricyclic analogues as well as the preliminary biological results are presented herein.
摘要
将结构多样性引入核苷支架中，将其作为潜在的化疗药物，一直以来都被认为是药物设计的重要方法。在这方面，我们设计并合成了一些创新的 2'-脱氧扩展核苷，其中在天然嘌呤支架的咪唑环和嘧啶环系统之间插入了一个杂芳族噻吩间隔环。本文介绍了实现扩展的 2'-脱氧鸟苷和 -腺苷三环类似物的合成努力以及初步的生物学结果。
相似文献
1
Synthesis and biological evaluation of a series of thieno-expanded tricyclic purine 2'-deoxy nucleoside analogues.一系列噻吩扩展三环嘌呤 2'-脱氧核苷类似物的合成与生物评价。
Bioorg Med Chem. 2012 May 1;20(9):3009-15. doi: 10.1016/j.bmc.2012.03.004. Epub 2012 Mar 12.
2
Synthesis and biological activity of 4'-thio-L-xylofuranosyl purine nucleosides.4'-硫代-L-木糖呋喃糖基嘌呤核苷的合成及生物活性
Nucleosides Nucleotides Nucleic Acids. 2005;24(10-12):1895-906. doi: 10.1080/15257770500269077.
3
Thiophene-expanded guanosine analogues of Gemcitabine.吉西他滨的噻吩扩展鸟苷类似物。
Bioorg Med Chem Lett. 2015 Oct 1;25(19):4274-6. doi: 10.1016/j.bmcl.2015.07.086. Epub 2015 Jul 30.
4
Hetero-expanded purine nucleosides. Design, synthesis and preliminary biological activity.杂环扩展嘌呤核苷。设计、合成及初步生物活性
Nucleic Acids Symp Ser (Oxf). 2008(52):635-6. doi: 10.1093/nass/nrn321.
5
Cytostatic and antiviral 6-arylpurine ribonucleosides. Part 7: synthesis and evaluation of 6-substituted purine l-ribonucleosides.细胞生长抑制和抗病毒的6-芳基嘌呤核糖核苷。第7部分：6-取代嘌呤1-核糖核苷的合成与评价。
Bioorg Med Chem Lett. 2006 Oct 15;16(20):5290-3. doi: 10.1016/j.bmcl.2006.07.092. Epub 2006 Aug 14.
6
Synthesis of a 3'-C-ethynyl-β-d-ribofuranose purine nucleoside library: Discovery of C7-deazapurine analogs as potent antiproliferative nucleosides.合成 3'-C-乙炔基-β-d-核糖呋喃嘌呤核苷文库：发现 C7-脱氮嘌呤类似物作为有效的抗增殖核苷。
Eur J Med Chem. 2018 Sep 5;157:248-267. doi: 10.1016/j.ejmech.2018.07.062. Epub 2018 Jul 29.
7
Synthesis and anti-hepatitis C virus (HCV) activity of 3'-C-substituted-methyl pyrimidine and purine nucleosides.3'-C-取代甲基嘧啶和嘌呤核苷的合成及抗丙型肝炎病毒（HCV）活性。
Bioorg Med Chem. 2010 Jul 1;18(13):4812-20. doi: 10.1016/j.bmc.2010.05.002. Epub 2010 May 31.
8
Synthesis and antiviral activity of 2'-deoxy-4'-thio purine nucleosides.2'-脱氧-4'-硫代嘌呤核苷的合成及其抗病毒活性
J Med Chem. 1996 Jan 19;39(2):538-42. doi: 10.1021/jm950701k.
9
Synthesis and biological activities of 2'-deoxy-2'-fluoro-4'-thioarabinofuranosylpyrimidine and -purine nucleosides.2'-脱氧-2'-氟-4'-硫代阿拉伯呋喃糖基嘧啶和嘌呤核苷的合成及生物活性
Bioorg Med Chem. 2000 Jul;8(7):1545-58. doi: 10.1016/s0968-0896(00)00065-1.
10
Synthesis of purine modified 2'-C-methyl nucleosides as potential anti-HCV agents.嘌呤修饰的 2'-C-甲基核苷的合成作为潜在的抗 HCV 药物。
Bioorg Med Chem Lett. 2011 Nov 15;21(22):6788-92. doi: 10.1016/j.bmcl.2011.09.034. Epub 2011 Sep 20.
引用本文的文献
1
Proximal fleximer analogues of 2'-deoxy-2'-fluoro-2'-methyl purine nucleos(t)ides: Synthesis and preliminary pharmacokinetic and antiviral evaluation.2'-脱氧-2'-氟-2'-甲基嘌呤核苷类似物的近端柔性类似物：合成及初步药代动力学和抗病毒评价。
Bioorg Med Chem. 2024 Oct 1;112:117898. doi: 10.1016/j.bmc.2024.117898. Epub 2024 Aug 24.
2
Probing the Effects of Pyrimidine Functional Group Switches on Acyclic Fleximer Analogues for Antiviral Activity.探究嘧啶官能团转换对无环构象限制分子类似物抗病毒活性的影响。
Molecules. 2019 Sep 2;24(17):3184. doi: 10.3390/molecules24173184.
3
The evolution of antiviral nucleoside analogues: A review for chemists and non-chemists. Part II: Complex modifications to the nucleoside scaffold.抗病毒核苷类似物的进化：化学家和非化学家的综述。第二部分：核苷骨架的复杂修饰。
Antiviral Res. 2019 Feb;162:5-21. doi: 10.1016/j.antiviral.2018.11.016. Epub 2018 Dec 8.
4
The evolution of nucleoside analogue antivirals: A review for chemists and non-chemists. Part 1: Early structural modifications to the nucleoside scaffold.核苷类似物抗病毒药物的演进：化学家与非化学家的综述。第 1 部分：核苷骨架的早期结构修饰。
Antiviral Res. 2018 Jun;154:66-86. doi: 10.1016/j.antiviral.2018.04.004. Epub 2018 Apr 10.
5
Flexibility-Not just for yoga anymore!灵活性——不再只是瑜伽的专属！
Antivir Chem Chemother. 2018 Jan-Dec;26:2040206618756788. doi: 10.1177/2040206618756788.
6
Thiophene-expanded guanosine analogues of Gemcitabine.吉西他滨的噻吩扩展鸟苷类似物。
Bioorg Med Chem Lett. 2015 Oct 1;25(19):4274-6. doi: 10.1016/j.bmcl.2015.07.086. Epub 2015 Jul 30.
7
Synthetic Routes to a Series of Proximal and Distal 2'-Deoxy Fleximers.一系列近端和远端2'-脱氧柔性体的合成路线。
Synthesis (Stuttg). 2012;44(22):3496-3504. doi: 10.1055/s-0032-1316791.
8
Effects of substitutions at the 4' and 2 positions on the bioactivity of 4'-ethynyl-2-fluoro-2'-deoxyadenosine.4'位和 2'位取代对 4'-乙炔基-2-氟-2'-脱氧腺苷生物活性的影响。
Antimicrob Agents Chemother. 2013 Dec;57(12):6254-64. doi: 10.1128/AAC.01703-13. Epub 2013 Oct 7.
9
Endo-S-c-di-GMP analogues-polymorphism and binding studies with class I riboswitch.内消旋-环二鸟苷单磷酸类似物-结构多态性与 I 类核糖体开关的结合研究。
Molecules. 2012 Nov 9;17(11):13376-89. doi: 10.3390/molecules171113376.
本文引用的文献
1
Synthesis and biological evaluation of 2',4'- and 3',4'-bridged nucleoside analogues.2',4'-和 3',4'-桥连核苷类似物的合成与生物评价。
Bioorg Med Chem. 2011 Sep 15;19(18):5648-69. doi: 10.1016/j.bmc.2011.07.022. Epub 2011 Jul 23.
2
Tricyclic 2'-C-modified nucleosides as potential anti-HCV therapeutics.三环 2'-C-修饰核苷类似物作为有潜力的抗 HCV 治疗药物。
Org Lett. 2010 Oct 15;12(20):4466-9. doi: 10.1021/ol101482h.
3
Antiretroviral drugs.抗逆转录病毒药物。
Curr Opin Pharmacol. 2010 Oct;10(5):507-15. doi: 10.1016/j.coph.2010.04.011. Epub 2010 May 12.
4
Mechanistic studies in the synthesis of a series of thieno-expanded xanthosine and guanosine nucleosides.一系列噻吩扩展的黄苷和鸟苷核苷合成的机理研究
Tetrahedron. 2008 Nov 24;64(48):10791-10797. doi: 10.1016/j.tet.2008.09.011.
5
Hetero-expanded purine nucleosides. Design, synthesis and preliminary biological activity.杂环扩展嘌呤核苷。设计、合成及初步生物活性
Nucleic Acids Symp Ser (Oxf). 2008(52):635-6. doi: 10.1093/nass/nrn321.
6
The discovery of antiviral agents: ten different compounds, ten different stories.抗病毒药物的发现：十种不同的化合物，十个不同的故事。
Med Res Rev. 2008 Nov;28(6):929-53. doi: 10.1002/med.20128.
7
Synthesis and properties of oligonucleotides with iodo-substituted aromatic aglycons: investigation of possible halogen bonding base pairs.含碘取代芳香糖苷配基的寡核苷酸的合成与性质：对可能的卤键碱基对的研究。
J Org Chem. 2008 Jan 18;73(2):383-90. doi: 10.1021/jo701634t. Epub 2007 Dec 15.
8
Synthesis and properties of size-expanded DNAs: toward designed, functional genetic systems.尺寸扩展DNA的合成与性质：迈向设计的功能性遗传系统
Acc Chem Res. 2007 Feb;40(2):141-50. doi: 10.1021/ar068200o.
9
New designs for DNA bases: expanded DNAs and oligofluorosides.DNA碱基的新设计：扩展DNA和寡氟化物。
Nucleic Acids Symp Ser (Oxf). 2006(50):15-6. doi: 10.1093/nass/nrl008.
10
Carbocyclic pyrimidine nucleosides as inhibitors of S-adenosylhomocysteine hydrolase.碳环嘧啶核苷作为S-腺苷同型半胱氨酸水解酶的抑制剂
Bioorg Med Chem. 2006 Dec 1;14(23):7967-71. doi: 10.1016/j.bmc.2006.07.052. Epub 2006 Aug 10.
Zotero 插件